Propagation of electrical impulses in the heart takes place as the result of an interaction between two processes: active generation of ionic currents across the cell membrane, and passive spread of current along cells and from cell-to-cell at specialized gap junctions. The goals of the proposed investigation are twofold: 1) to develop a computer model of electrical propagation in cardiac tissue; and 2) to use that model in understanding the mechanism of cardiac arrhythmias in a way not possible using traditional techniques and biological preparations. Normally, an orderly flow of electrical activity emanates from the sinus node to engage the remainder of the heart. However, under pathological conditions pathways can be established which allow the cardiac impulse to recirculate, thus usurping control from the sinus mechanism. Such an arrhythmia is termed "reentry". Substantial evidence favors reentry as responsible for sustained ventricular tachycardia (VT) in patients with healed myocardial infarctions. The reentry circuit occupies a relatively circumscribed volume in the border zone between normal and infarcted muscle. However, the exact mechanism through which the required electrical circuit develops in hearts scarred by prior myocardial infarction is not known. In the proposed investigation we will try to understand how the electrophysiologic conditions for reentry are met in the setting of chronic myocardial infarction by using a computer model of heterogeneously scarred ventricular muscle. In particular, we hypothesize that abnormal cell-to- cell electrical coupling plays a primary role in allowing the initiation and perpetuation of reentrant tachycardia, without the need to invoke abnormal membrane ionic properties such as the sodium current. A realistic numerical model of two-dimensional sheet of myocardium will be used to examine how small-scale perturbations in the pattern of electrical interaction between cells leads to uncontrolled recirculation of electrical propagation. A three-dimensional color animated display will aid in visualizing and correlating the large quantify of data available from such a model. The proposed investigation is important in providing the theoretical basis needed for more effective treatment of the ventricular arrhythmias that kill 400,000 persons yearly. If correct, our hypothesis that abnormal coupling is the primary defect leading to VT in chronic infarction may require new approaches to treatment. For example, how antiarrhythmic drugs effect cellular coupling may be more important in predicting benefit than their effects on membrane properties such as the sodium or calcium current. Theoretically, a new class of drugs which acts by completely uncoupling cells with infarct-induced tenuous coupling could normalize heterogenous conduction and refractoriness, and thereby offer a new approach to pharmacologic therapy of arrhythmias. Computer modeling of electrical propagation in infarcted myocardium will offer insight into the mechanism of reentrant VT not possible in biological preparations.